Functional evaluation of iPS cell-derived periodontal ligament-like cells

Periodontal ligament (PDL) is essential in supporting tooth, remodeling, and regeneration of periodontal tissues; however, donor-derived PDL cells have limited regenerative applications. We previously developed a method to generate PDL-like cells from induced pluripotent stem (iPS) cells using PDL-conditioned medium. In this study, we validated whether iPS-derived PDL cells (iPS-PDL) recapitulate established functions of PDL cells. Morphologically, iPS-PDL resembled primary PDL cells and exhibited a higher proliferative capacity. They expressed PDL-related genes, such as Periostin, Asporin, and Tenascin-C, at levels exceeding those of fibroblasts. Under osteogenic induction, iPS-PDL deposited a mineralized matrix and upregulated the expression of COL1A1, ALPL, OCN, and RUNX2. Ascorbic acid enhanced ALP activity and collagen synthesis, while compressive force induced IL6, IL1β, and COX2 expression, These findings demonstrate that iPS-PDL retain PDL-like functions and are a promising cell source for periodontal regeneration, offering the potential for both therapeutic applications and in vitro modeling of periodontal biology.